Morphic forms of danicopan

Abstract

This invention provides stable, highly crystalline forms of Complement factor D inhibitors Compound 1 for advantageous therapeutic pharmaceutical efficacy and dosage form stability.

We claim: 
     
       1. An isolated crystalline Form II of Compound 1: 
       
         
           
           
               
               
           
         
       
       characterized by a powder X-ray diffraction (PXRD) pattern comprising at least five 2theta values selected from 5.1±0.2°, 7.8±0.2°, 13.5±0.2°, 14.0±0.2°, 15.4±0.2°, 15.6±0.2°, 18.6±0.2°, 20.5±0.2°, 20.7±0.2°, and 23.4±0.2°. 
     
     
       2. The isolated crystalline Form II of  claim 1 , wherein the PXRD pattern comprises at least six 2theta values selected from 5.1±0.2°, 7.8±0.2°, 13.5±0.2°, 14.0±0.2°, 15.4±0.2°, 15.6±0.2°, 18.6±0.2°, 20.5±0.2°, 20.7±0.2°, and 23.4±0.2°. 
     
     
       3. The isolated crystalline Form II of  claim 1 , wherein the PXRD pattern comprises at least seven 2theta values selected from 5.1±0.2°, 7.8±0.2°, 13.5±0.2°, 14.0±0.2°, 15.4±0.2°, 15.6±0.2°, 18.6±0.2°, 20.5±0.2°, 20.7±0.2°, and 23.4±0.2°. 
     
     
       4. The isolated crystalline Form II of  claim 1 , wherein the PXRD pattern comprises at least eight 2theta values selected from 5.1±0.2°, 7.8±0.2°, 13.5±0.2°, 14.0±0.2°, 15.4±0.2°, 15.6±0.2°, 18.6±0.2°, 20.5±0.2°, 20.7±0.2°, and 23.4±0.2°. 
     
     
       5. The isolated crystalline Form II of  claim 1 , wherein the PXRD pattern comprises at least nine 2theta values selected from 5.1±0.2°, 7.8±0.2°, 13.5±0.2°, 14.0±0.2°, 15.4±0.2°, 15.6±0.2°, 18.6±0.2°, 20.5±0.2°, 20.7±0.2°, and 23.4±0.2°. 
     
     
       6. The isolated crystalline Form II of  claim 1 , wherein the PXRD pattern comprises 2theta values selected from 5.1±0.2°, 7.8±0.2°, 13.5±0.2°, 14.0±0.2°, 15.4±0.2°, 15.6±0.2°, 18.6±0.2°, 20.5±0.2°, 20.7±0.2°, and 23.4±0.2°. 
     
     
       7. The isolated crystalline Form II of  claim 1 , wherein the PXRD pattern comprises at least the 2theta value of 5.1±0.2°. 
     
     
       8. The isolated crystalline Form II of  claim 1 , wherein the PXRD pattern comprises at least the 2theta value of 14.0±0.2°. 
     
     
       9. The isolated crystalline Form II of  claim 1 , wherein the PXRD pattern comprises at least the 2theta value of 15.4±0.2°. 
     
     
       10. The isolated crystalline Form II of  claim 1 , having the 2theta values of  FIG.  4 C . 
     
     
       11. The isolated crystalline Form II of  claim 1 , characterized by a differential scanning calorimetry (DSC) endotherm from about 40° C. to about 125±20° C. 
     
     
       12. The isolated crystalline Form II of  claim 1 , characterized by a differential scanning calorimetry (DSC) endotherm of about 155° C. 
     
     
       13. A pharmaceutical composition comprising the isolated crystalline Form II of  claim 1  in a pharmaceutically acceptable excipient for solid dosage delivery. 
     
     
       14. A method of inhibiting Complement Factor Din a subject in need thereof comprising administering to the subject in need thereof a therapeutically effective amount of the isolated crystalline Form II of  claim 1 . 
     
     
       15. The method of  claim 14 , wherein the subject is a human.